Effect of APOE and LPA genotypes on the risk of dementia after myocardial infarction: a clinic-based cohort study

Survivors of myocardial infarction (MI) face elevated risk of subsequent cognitive decline, yet the relative contributions of neurodegenerative susceptibility ( APOE4 ) and lipid-mediated vascular burden ( LPA risk variants) to post-MI dementia remain unclear, particularly in Asian populations historically underrepresented in dementia genetics research. We conducted a retrospective cohort study of 4,788 patients with confirmed MI enrolled in the China Medical University Hospital precision medicine program (January 1, 2004–December 31, 2021), with directly genotyped APOE (rs429358, rs7412) and LPA (rs10455872, rs3798220) variants linked to longitudinal electronic health records and the Taiwan National Death Registry. Patients were classified into four genetic risk groups: low-risk, LPA -only, APOE4-only, and dual-risk. The primary outcome was incident all-cause dementia within a fixed 5-year follow-up and was analyzed using Cox proportional hazards regression. Sensitivity analyses included a Fine–Gray subdistribution hazards model to describe the cumulative incidence of dementia in the presence of death as a competing event, along with subgroup analyses by age, sex, and cardiovascular comorbidity. The median age was 61.2 years (IQR 51.9–70.3). Compared with the low-risk reference, APOE4 carriers had substantially elevated dementia risk ( APOE4- only: HR 2.49, 95% CI 1.71–3.63; dual-risk: HR 2.63, 95% CI 1.32–5.26), whereas LPA -only carriers did not (HR 1.19, 95% CI 0.73–1.95). Five-year dementia-free survival approached 96% in the low-risk and LPA -only groups, declined to approximately 93% in the APOE4 -only group, and was lowest in dual-risk carriers. Kaplan–Meier curves showed accelerated divergence among APOE4 carriers at approximately 840 days post-MI. Associations were consistent across age (< 65 vs. ≥ 65 years; interaction p = 0.389) and sex (interaction p = 0.141) and remained robust in Fine–Gray competing-risk analyses. Among MI survivors in a real-world Asian genomic cohort, APOE4, but not LPA, was associated with subsequent dementia, suggesting a greater role for neurodegenerative susceptibility than Lp(a)-related lipid-vascular burden in post-MI cognitive outcomes. The apparent risk divergence around 840 days after MI remains exploratory and warrants further study.